AP Group Research Articles

Fibrinogen-Like Protein 2 Protects the Aggravation of Hypertriglyceridemia on the Severity of Hypertriglyceridemia Acute Pancreatitis by Regulating Macrophages.

The mechanisms underlying the increased severity of hypertriglyceridemia acute pancreatitis (HTG-AP) remain poorly understood. Fibrinogen-like protein 2 (FGL2) has been identified as a regulator of macrophage activity, mediating immune suppression. This study aims to examine the role of FGL2 in the susceptibility to severe conditions of HTG-AP. Both wild-type and FGL2 gene knockout C57BL/6 mice were utilized to establish HTG, AP, and HTG-AP models using P-407 and/or caerulein. Serum levels of triglycerides, total cholesterol, amylase, and lipase were assessed via biochemical analysis. Pancreatic and lung tissue injuries were evaluated using hematoxylin and eosin staining. Tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β), and interleukin-6 (IL-6) levels in serum and pancreatic tissues were quantified using enzyme-linked immunosorbent assay (ELISA). Immunohistochemistry was used to assess the expression of FGL2, the macrophage marker CD68, and M1/M2 macrophage markers iNOS/CD163. The animal models were successfully established. Compared to wild-type mice, FGL2 knockout resulted in increased pathological injury scores in the pancreas and lungs, as well as elevated TNF-α, IL-1β, and IL-6 levels in serum and pancreatic tissue in the HTG group, with more pronounced effects observed in the HTG-AP group. The AP group alone did not exhibit significant changes due to FGL2 knockout. Further analysis revealed that FGL2 knockout increased CD68 expression but reduced CD163 expression in the pancreatic tissues in the HTG group. In the HTG-AP group, there was a marked increase in CD68 and iNOS expressions, coupled with a reduction in CD163 expression. FGL2 knockout in HTG and HTG-AP mice resulted in increased inflammatory responses and a significant imbalance in M2 macrophages. These findings suggest that FGL2 plays a crucial role in mitigating the aggravation of HTG on the severity of HTG-AP by modulating macrophage activity.

Comparison of the Safety of Aspirin Monotherapy and Aspirin and P2Y12 Inhibitor Combination Therapy in Patients Post Coil Embolization During Admission: A Cross-Sectional Study Using a Nationwide Inpatient Database.

Some aspects regarding the use of antiplatelet agents after coil embolization for subarachnoid hemorrhage during admission remain unclear. This study used diagnostic procedure combination (DPC) data to investigate the safety and prognostic effects of aspirin monotherapy and aspirin and P2Y12 inhibitor combination therapy on bleeding events. This cross-sectional study used Japanese DPC data to assess patients who were hospitalized with subarachnoid hemorrhage and received aspirin monotherapy and aspirin and P2Y12 inhibitor combination therapy between April 2016 and March 2020 (n = 4421). The aspirin monotherapy (A group, n = 2848) and aspirin and P2Y12 inhibitor combination therapy (AP group, n = 1573) groups were compared. The primary and secondary endpoints were the incidence of bleeding events and proportion of patients with a modified Rankin Scale (mRS) score ≤ 2 at discharge, respectively. Data was analyzed using multivariable adjusted logistic regression (significance level, 5%). The adjusted odds ratio in AP group, with A group as the reference, for bleeding events and the proportion of patients with mRS score ≤ 2 at discharge were 0.97 (95% confidence interval [95% CI]: 0.75-1.26, p = 0.839) and 1.09 (95% CI: 0.92-1.29, p = 0.302), respectively. There are no differences in the incidence of bleeding events or good clinical outcomes (mRS score ≤ 2 at discharge) between aspirin monotherapy and aspirin and P2Y12 inhibitor combination therapy.

Study of the Effects of Alfalfa Bioactive Substances and Polysaccharides on the Lactation Performance and Immune Function of Dairy Cows

Background: The aim of this study was to investigate the effects of alfalfa polysaccharides on the lactation performance and immune function of dairy cows. Methods: A total of 84 healthy Holstein cows were selected and randomly divided into 7 groups, including the control Group A0, the alfalfa polysaccharide groups (AP1, AP2, AP3) and the alfalfa extract groups (AE1, AE2, AE3). Each group had three replicates and each replicate had four cows. The daily rations of the dairy cows in the AP group and the AE group were supplemented with alfalfa polysaccharide powder and alfalfa extract at concentrations of 1, 2 and 3 kg/t, those in the A0 group served as a control. Result: (1) the milk production of dairy cows in the AE groups was extremely significantly greater (p less than 0.01) than that in A0 group and AP groups. The milk protein content of cows in the AP2 and AE2 groups was significantly greater (P less than 0.05) than that in the A0 group (2) The interleukin-2 (IL-2) levels in the serum of cows in the AP2, AP3, AE2 and AE3 groups were greater than those in the A0 and AP1 groups and the IgM antibody levels in the AP group and the AE group were extremely significantly greater than those in the A0 and AP1 groups (P less than 0.01). The IgA antibody level in the serum of dairy cows in the AP2, AP3, AE2 and AE3 groups was significantly (P less than 0.01) greater than that in the A0, AP1 and AE1 groups. In summary, the alfalfa extract improved both the lactation performance and immunity of dairy cows, indicating comprehensive effects. Alfalfa polysaccharides at a concentration of 2 kg/t improved the immunity of dairy cows.

Study on the Microbial Mechanisms of Enhancing Agaricus bisporus Growth through Inoculation with Pseudomonas putida

Introducing Pseudomonas putida optimizes the microbial community within the casing layer, thereby enhancing Agaricus bisporus growth. Nevertheless, the underlying mechanisms governing microbial community succession within the casing layer following microbial agent introduction remained elusive. This study delineated the interplay among microbial populations in the casing layer across the growth cycle of A. bisporus, comparing cohorts treated with P. putida (AP) against untreated controls (CK). The inoculation with Pseudomonas promoted the growth of A. bisporus, shortened its growth cycle, and linearly enhanced the relative abundance of key bacterial genera integral to its growth, including Flavobacterium, Rhodoferax, Pseudarthrobacter, and Vogesella (adjusted R2=0.238-0.866). Importantly, a positive correlation was identified between the proliferation of these beneficial bacteria and positive community cohesion (adjusted R2=0.353-0.838). Additionally, analysis of the symbiotic network topology within the AP group indicated a more stable community following inoculation. The niche results (AP=11.7672±1.8938, CK=11.0481±3.1273, P<0.05) underscored the positive impact of Pseudomonas inoculation on ecosystem dynamics. Concentrations of essential nutrients for A. bisporus growth, notably readily available phosphorus (On day 17, the AP group was 78.8333±1.26623 mg/kg, while the CK group was 30.0333±0.98658 mg/kg) and readily available potassium (On day 17, the AP group was 2693.9±14.79561 mg/kg, while the CK group was 1646.9333±10.71276mg/kg), were significantly elevated in the AP group. These enhancements strongly correlated with the increased abundance of pivotal microbial populations. Our research provided insights into the application of microbial inoculants to enhance the production of edible fungi.

A Prospective Comparative Study on the Clinical Diagnostic Performance of Blood Inflammatory Markers in Acute Appendicitis.

Despite the substantial advancements in imaging techniques for the diagnosis and differential diagnosis of acute appendicitis (AA) over recent decades, the specificity and sensitivity of widely utilized laboratory biomarkers in clinical practice remain inadequate.This study aimed to investigate the diagnostic utility of commonly employed blood inflammatory markers for AA. A total of 399 participants who either sought medical care or underwent health examinations were enrolled in this prospective study. The cohort comprised 200 patients diagnosed with AA (AA group), 100 patients presenting with abdominal pain but without AA (AP group), and 99healthy individuals undergoing routine health check-ups (HC group). For all subjects, the following biomarkers were measured: plasma neutrophil gelatinase-associated lipocalin (NGAL), white blood cell count (WBC), neutrophil count (NEU), percentage of neutrophils (NEU%), neutrophil-to-lymphocyte ratio (NLR), and C-reactive protein (CRP). The diagnostic performance of the observed indicators, both individually and in combination, was assessed for the diagnosis of AA using Receiver Operating Characteristic (ROC) curves analysis and Delong's test. The laboratory indicators demonstrated a progressive increase from the HC group to the AP group, and further to the AA group (all p<0.05). Multifactorial logistic regression analysis identified NEU% and plasma NGAL as significant risk factors for the occurrence of AA. ROC curve analysis and Delong's test indicated that, in distinguishing the AA group from the HC group, the diagnostic performance of plasma NGAL, CRP, and NLR was equally substantial and superior to that of NEU and WBC. Within the AP group, plasma NGAL and CRP exhibited comparable diagnostic efficacy, outperforming NEU, WBC, and NLR. When differentiating AA in the non-appendicitis group (ie HC group + AP group), NGAL and CRP demonstrated comparable diagnostic efficacy, surpassing that of NEU, white WBC, and NLR. While the integration of multiple diagnostic tests can potentially improve overall diagnostic accuracy, the observed enhancement in the AUC is not statistically significant. NGAL, CRP, WBC, NEU% and NLR were significantly increased in patients with acute abdomen. NGAL and NEU% may function as independent risk factors for predicting the incidence of AA, with NGAL and CRP demonstrating similar and favorable diagnostic performance. While the combined evaluation of these biomarkers may enhance the diagnostic value for AA, the improvement in the area under the curve (AUC) is not substantial.

Dietary starch structure modulates nitrogen metabolism in laying hens via modifying glucose release rate

The objective of this study was to investigate the effects of starch structure (Amylopectin/Amylose, AP/AM) in a low-protein diet on production performance, nitrogen utilization efficiency, and cecal flora in laying hens. Four hundred eighty 45-wk-age Hy-Line Gray laying hens were randomly allocated to five dietary groups and subjected to a 12-wk feeding trial. The AP/AM ratios of the five experiment diets were 1.0, 1.5, 2.0, 3.0, and 4.0. The results indicated that compared to other groups, laying hens fed with AP/AM 4.0 diets showed significantly improved average egg weight and feed conversion ratio (P < 0.05). Furthermore, as the AP/AM ratio increased, there was a significant linear enhancement in intestinal amino acids apparent digestibility, apparent metabolizable energy, and villus area (P < 0.05). Compared to the high AP groups, high-AM diets significantly increased eggshell thickness, crude protein digestibility, and reduced energy supply from amino acid oxidation in ileum (P < 0.05). Additionally, moderate-AM diets enriched with short-chain fatty acid-producing bacteria in the cecum, such as Lactobacillus, Rikenellaceae_RC9_gut_group, and Christensenellaceae_R-7_group, which are associated with the promoting nitrogen utilization. These findings may offer useful information on optimizing starch structure for the design of food products and relevant therapies due to the potential effects on nutrient metabolism and gut homeostasis.

Evaluation of the Effects of Repetitive Anaesthesia Administration on the Brain Tissues and Cognitive Functions of Rats with Experimental Alzheimer's Disease.

Introduction: We evaluated the effects of repeated ketamine, propofol, and ketamine + propofol administration on cognitive functions and brain tissue of elderly rat models with streptozotocin-induced Alzheimer's disease. Materials and Methods: Thirty elderly male Wistar Albino rats were divided into five groups: control (Group C), Alzheimer's (Group A), Alzheimer's + ketamine (Group AK), Alzheimer's + propofol (Group AP), and Alzheimer's + propofol + ketamine (Group APK). Alzheimer's disease was induced in Groups A, AK, AP, and APK via intracerebroventricular streptozotocin. Four weeks after surgery, ketamine, propofol, and ketamine + propofol were administered intraperitoneally for 3 days to Groups AK, AP, and APK, respectively. The radial arm maze test (RAMT) was performed in the initial, 1st, 2nd, 3rd, and 4th weeks after surgery and daily following anaesthesia. Blood and brain tissue samples were obtained. Results: The RAMT results of Groups A, AK, AP, and APK decreased compared to Group C 2 weeks after Alzheimer's disease onset. Compared to Group A, the RAMT results increased in Groups AK and APK after the first anaesthesia, and in Group AP after the second anaesthesia. Brain tissue paraoxonase-1 (PON-1) and catalase (CAT) activities were low, and the thiobarbituric acid reactive substance (TBARS) level was high in Group A compared to Group C. TBARS levels of Groups AP and APK were lower than Group A, while CAT activity was higher. PON-1 activity was higher in Groups AK, AP, and APK than in Group A. Histopathological changes decreased in Groups AP and AK. A decrease in p53 was found in Group C compared to Group A. Ketamine and propofol were found to be effective at Bcl-2 immunoexpression, but a decrease in Caspase-3 was observed in Group APK. GFAP immunoexpression increased in Group A compared to Group C and in Group AP compared to Group AK. Conclusions: Repetitive anaesthesia application was found to positively affect cognitive functions. This was supported by histopathological and biochemical markers.

Comparison of Therapeutic Effect of Apheresis Platelets and Buffy Coat-Derived Platelet Concentrates.

The study aimed to investigate the difference in clinical efficacy between apheresis platelets and buffy coat-derived platelet concentrates infusion in patients with hematological diseases. A total of 218 patients with hematological diseases were enrolled in Xi'an Central Hospital, from January 2023 to October 2023, and randomly divided into two groups: 109 patients were treated with apheresis platelet transfusion (AP group) and 109 patients with buffy coat derived platelet concentrates (BC-PC group). Platelet counts were measured before and 24 hours after transfusion, and the corrected platelet ascending number (CCI) and platelet recovery rate (PPR) were calculated. The clinical efficacy and blood transfusion reaction were observed. After 24 hours of platelet transfusion, there was no significant difference in the platelet count between the AP and BC-PC groups (p > 0.05). However, CCI and PPR significantly differed between the two groups (p < 0.05). Moreover, the incidence of transfusion reaction in the AP group was significantly lower than in the BC-PC group. The clinical efficacy of buffy coat-derived platelet concentrates is lower than that of apheresis platelets, but it can also improve the patient's condition and quality of life. Therefore, clinicians could rationally use BC-PC, according to the actual situation of the patients.

Comparison of Complication Rates Between Transforaminal Interbody Fusion and Anteroposterior Fusion for One- or Two-Level Degenerative Lumbar Spine Surgery: A Propensity Score Matched Analysis.

Introduction Although transforaminal interbody fusion (TLIF) and anterior lumbar interbody fusion (ALIF) combined with posterior fusion (AP) have similar fusion rates, it is unclear if choice of approach has an impact on post-operative complications. Research question Is the incidence of residual leg and/or back pain requiring additional treatment after one- or two-level TLIF and AP similar? Material and methods Adult patients who underwent one- or two-level TLIF or AP for degenerative pathology were identified and matched using age, sex, body mass index (BMI), American Society of Anesthesiologists (ASA), insurance status, smoking status, revision and number of levels fused. The incidence of radicular leg and back pain requiring emergency department visit/readmission or same level surgical intervention was compared between the two groups. Results Of the 319 TLIF and 288 AP cases, 119 cases in each cohort were matched. TLIF patients had shorter operative times (203 min vs 258 min, P<0.001) and hospital stays than the AP patients (3.76 days vs 4.98 days, P<0.001). The incidence of residual leg pain (7 vs 5, P=0.769) and back pain (13 vs 15, P=0.841) was similar between the two groups. Except for constipation, which was more common in the AP group, the incidence of complications was similar between the two groups. Conclusions Patients undergoing one- or two-level TLIF showed shorter operative time and hospital stay compared with those undergoing AP. The incidence of leg radiculopathy and back pain was similar between the two groups. Surgeons should consider these findings as part of the decision-making process regarding which approach to use in patients requiring a lumbar interbody fusion.

Deep cervical lymph nodes in Parkinson's disease and atypical Parkinson's disease: A potential ultrasound biomarker for differential diagnosis.

Parkinson's disease (PD) is a common degenerative disease caused by abnormal accumulation of α-synuclein. The glymphatic pathway is essential for removing macromolecular proteins including α-synuclein from the brain, which flows into deep cervical lymph nodes (DCLNs) through meningeal lymphatics. As a terminal station for the cerebral lymphatic system drainage, DCLNs can be easily assessed clinically. Although the drainage function of the cerebral lymphatic system is impaired in PD, the correlation between DCLNs and PD remains unknown. Single-center retrospective cross-sectional study. The size of the DCLNs were measured using ultrasound. The Movement Disorder Society Sponsored Revision Unified Parkinson's Disease Rating Scale and other scales were used to assess PD motor and non-motor symptoms. Compared with the healthy control (HC) and the atypical Parkinson's disease (AP) groups, the size of the second and third DCLNs in the Parkinson's disease (PD) group was significantly smaller (P < .05). The width diameter of the third DCLN (DCLN3(y)) was significantly smaller in the PD group than in the AP group (P = .014). DCLN3(y) combined with a variety of clinical features improved the sensitivity of AP identification (sensitivity = .813). DCLNs were able to distinguish HC, PD and AP and were mainly located in Robbins ΙΙA level. PD and AP were associated with different factors that influenced the size of the DCLNs. DCLN3(y) plays an important role in differentiating PD from AP, which, combined with other clinical features, has the ability to distinguish PD from AP; in particular, the sensitivity of AP diagnosis was improved.

Acute Effects of Dietary Protein Consumption on the Postprandial Metabolic Response, Amino Acid Levels and Circulating MicroRNAs in Patients with Obesity and Insulin Resistance.

The post-nutritional intervention modulation of miRNA expression has been previously investigated; however, post-acute dietary-ingestion-related miRNA expression dynamics in individuals with obesity and insulin resistance (IR) are unknown. We aimed to determine the acute effects of protein ingestion from different dietary sources on the postprandial metabolic response, amino acid levels, and circulating miRNA expression in adults with obesity and IR. This clinical trial included adults with obesity and IR who consumed (1) animal-source protein (AP; calcium caseinate) or (2) vegetable-source protein (VP; soy protein isolate). Glycaemic, insulinaemic, and glucagon responses, amino acid levels, and exosomal microRNAs isolated from plasma were analysed. Post-AP ingestion, the area under the curve (AUC) of insulin (p = 0.04) and the plasma concentrations of branched-chain (p = 0.007) and gluconeogenic (p = 0.01) amino acids increased. The effects of different types of proteins on the concentration of miRNAs were evaluated by measuring their plasma circulating levels. Compared with the baseline, the AP group presented increased circulating levels of miR-27a-3p, miR-29b-3p, and miR-122-5p (p < 0.05). Subsequent analysis over time at 0, 30, and 60 min revealed the same pattern and differences between treatments. We demonstrated that a single dose of dietary protein has acute effects on hormonal and metabolic regulation and increases exosomal miRNA expression in individuals with obesity and IR.

Effects of pregabalin combined with tramadol/paracetamol on acute pain in patients with CT-guided puncture localization of pulmonary nodules

ObjectiveTo investigate the effects of pregabalin combined with tramadol/paracetamol on acute pain in patients with CT-guided puncture localization of pulmonary nodules. Materials and MethodsIn this randomized, placebo-controlled and single-center study, 120 patients were allocated randomly to four groups: the control group (Group P), the pregabalin-placebo group (Group BP), the tramadol/paracetamol-placebo group (Group AP), and the pregabalin-tramadol/paracetamol group (Group AB). The primary outcome was the NRS (Numerical Rating Scale) score. Other outcomes included systolic blood pressure (SBP), diastolic blood pressure (DBP), heart rate (HR), pulse oxygen saturation (SpO2), the incidence of moderate to severe pain, the analgesia recovery ratio, the incidence of adverse drug reactions and patients’ satisfaction. ResultsNo significant interaction was detected between the interventions (P = 0.752). The NRS score of the Taking pregabalin group and the Taking tramadol/paracetamol group were significantly lower than those of the Not-taking pregabalin group and the Not-taking tramadol/paracetamol group respectively (P < 0.05). There was significant difference in the NRS scores among the four groups (P < 0.001). The NRS score of Group AB was significantly lower than that of Group P (P < 0.001), Group BP (P < 0.001) and Group AP (P = 0.001). At the same time, the NRS scores of Group BP (P < 0.001) and Group AP (P < 0.001) were significantly lower than those of Group P, but there was no significant difference between Group BP and Group AP (P = 1.000). The SBP, DBP, HR, the incidence of moderate to severe pain and the analgesia recovery ratio of Group AB were significantly lower than those of Group P (P < 0.05), while the SpO2 and the number of people who were very satisfied were significantly higher than those of Group P (P < 0.05). There was no significant difference in the incidence of adverse drug reactions among the four groups (P = 0.272). ConclusionsThe combination or single use of pregabalin and tramadol/paracetamol can effectively relieve the acute pain after localization. Pregabalin combined with tramadol/paracetamol has the best analgesic effect and significantly reduces the hemodynamic fluctuations, with high safety and low incidence of adverse drug reactions, which has a certain clinical popularization and application value.

Effect of Rearing Technology on Production Performance, Selected and Blood Parameters and Welfare Levels of Broiler Chickens During the Summer Production Cycle

Abstract The aim of the present study was to determine the effect of rearing technology (rearing system and dietary supplementation with a mixed herbal extract) on the production results, selected physiological and blood parameters, and welfare of broiler chickens during the summer production cycle. In the CON and HE groups, broiler chickens were kept on litter without access to free range; additionally, in the HE group, birds from 22 to 42 days of rearing received a mixed herbal extract (50% Melissa officinalis L. and 50% Urtica dioica L.) in the amount of 2 ml/l of water to drinkers with water. In the AP group, birds were reared on litter with access to pasture. During the experiment, production performance and body temperature of the birds were monitored. Blood was also taken from birds in each group and the H:L ratio, levels of corticosterone, glucose and thyroid hormones were determined. The application of 2 ml/l of mixed herbal extract to the drinking water did not improve the production results, nor did it affect the physiological indices of the birds studied. The addition of 2 ml/l of mixed herbal extract to the drinking water only resulted in lower corticosterone levels in the blood of the chickens on day 35 of the experiment. The free-range housing system had a negative effect on the slaughter performance of the broiler chickens. However, housing with access to the free range resulted in lower body temperature, lower mortality, as well as lower glucose, corticosterone and a narrower H:L ratio in the blood of the chickens during the period of increasing air temperature. It can therefore be concluded that housing with access to a free range reduces stress levels and thus improves the welfare of broiler chickens during the summer production cycle compared to confined housing. Comparing the rearing technologies used in the study, it was found that the free-range housing system contributed more to improving the comfort of broiler chickens during the summer than dietary supplementation with the tested herbal mixture extract.

Severity and Prevalence in Non-Specific Interstitial Pneumonia and COVID-19 Associated Pneumonia

Background: The non-specific clinical presentation and absence of definitive diagnostic markers further complicate the diagnosis of nterstitial lung diseases (ILD), particularly idiopathic interstitial pneumonia (IIP). This study aimed to investigate the clinical and epidemiological characteristics, along with imaging diagnostics, of patients with non-specific interstitial pneumonia (NsIP) in the Samarkand region from 2020 to 2023. Methods: A retrospective analysis of medical records was conducted for 262 patients diagnosed with ILD and hospitalized at the Samarkand State Medical Association (SamSMA). Using a multidisciplinary approach and adhering to the international classification of diseases (ICD-10) criteria, patients were categorized into two groups: those diagnosed with NsIP and a comparison group of patients with COVID-19-associated pneumonia (COVID-19 AP). The patients were further subdivided based on disease severity: moderate (IA) and severe (IB) for the NsIP group, and moderate (IIA) and severe (IIB) for the COVID-19 AP group. Results: The study found that 72.5% of ILD patients had NsIP, predominantly older males. Moderate disease severity was more common in NsIP patients, while severe cases were more prevalent in the COVID-19 AP group. The age groups 45-59 and 60-74 years represented 78% of the NsIP cases. Conclusion: The study found a higher prevalence of NsIP among men, with the majority of cases occurring in older age groups. Moderate disease severity was more common in NsIP patients, contrasting with COVID-19 AP patients, where severe cases were more prevalent.

Investigation of Cytokines, Biochemical Parameters and Oxidative Stress Levels in Serum of Patients with Acute Pancreatitis

Objective: This study aimed to find new serum biochemistry parameters, especially for the early identification of severe AP. In the study serum cytokine levels (TNF-A, IL-1, IL-6, IL-10, IL-21), biochemical parameters (Aquaporin-1, Hepcidine, Iron, Zinc, Copper, Nitric Oxide, C-Reactive protein), and oxidative stress parameters analysis were performed. Method: A total of 46 patients with AP and 46 healthy controls were included in this study. Serum cytokine levels, biochemical, and oxidative stress parameters by the ELISA method, and CRP by the immunoturbidimetric method were measured. Results: When patients with AP and control groups were compared, all studied parameters were found to be statistically significant (p&amp;lt;0.05). However, IL-1 was found to be insignificant (p&amp;gt;0.05). Therefore, the Mann-Whitney U test, which is a non-parametric test, was found suitable to determine whether there was a significant difference between the patient and control groups. Conclusions: Investigating the role of cytokines, oxidative stress and other biochemical parameters in the pathogenesis and course of the disease may contribute to a better understanding of the disease process and its therapeutic value. It showed a significant increase in oxidative stress parameters and biochemical parameters such as aquaporin-1, hepcidin, lipase, and amylase, which may help in the diagnosis of AP.

Artificial periosteum promotes bone regeneration through synergistic immune regulation of aligned fibers and BMSC-recruiting phages

Given the crucial role of periosteum in bone repair, the use of artificial periosteum to induce spontaneous bone healing instead of using bone substitutes has become a potential strategy. Also, the proper transition from pro-inflammatory signals to anti-inflammatory signals is pivotal for achieving optimal repair outcomes. Hence, we designed an artificial periosteum loaded with a filamentous bacteriophage clone named P11, featuring an aligned fiber morphology. P11 endowed the artificial periosteum with the capacity to recruit bone marrow mesenchymal stem cells (BMSCs). The artificial periosteum also regulated the immune microenvironment at the bone injury site through the synergistic effects of biochemical factors and topography. Specifically, the inclusion of P11 preserved inflammatory signaling in macrophages and additionally facilitated the migration of BMSCs. Subsequently, aligned fibers stimulated macrophages, inducing alterations in cytoskeletal and metabolic activities, resulting in the polarization into the M2 phenotype. This progression encouraged the osteogenic differentiation of BMSCs and promoted vascularization. In vivo experiments showed that the new bone generated in the AP group exhibited the most efficient healing pattern. Overall, the integration of biochemical factors with topographical considerations for sequential immunomodulation during bone repair indicates a promising approach for artificial periosteum development. Statement of significanceThe appropriate transition of macrophages from a pro-inflammatory to an anti-inflammatory phenotype is pivotal for achieving optimal bone repair outcomes. Hence, we designed an artificial periosteum featuring an aligned fiber morphology and loaded with specific phage clones. The artificial periosteum not only fostered the recruitment of BMSCs but also achieved sequential regulation of the immune microenvironment through the synergistic effects of biochemical factors and topography, and improved the effect of bone repair. This study indicates that the integration of biochemical factors with topographical considerations for sequential immunomodulation during bone repair is a promising approach for artificial periosteum development.

Analysis of inflammation and bone remodeling of atmospheric plasma therapy in experimental periodontitis.

The biological effects of atmospheric plasma (cold plasma) show its applicability for controlling the etiological factors that involve tissue repair. Thus, the study evaluated the effect of atmospheric plasma therapy in the control of tissue inflammation and bone remodeling in experimental periodontitis. Fifty-six rats were subjected to ligation in the cervical region of the first maxillary molars (8 weeks). The animals were divided into two groups (n = 28): periodontitis without treatment group (P group), and periodontitis with atmospheric plasma treatment group (P + AP group). Tissue samples were collected at 2 and 4 weeks after treatment to analyze the inflammation and bone remodeling by biochemical, histomorphometric, and immunohistochemical analyses. Inflammatory infiltration in the gingival and periodontal ligament was lower in the P + AP group than in the P group (p < .05). The MPO and NAG levels were higher in the P + AP group compared to P group (p < .05). At 4 weeks, the TNF-α level was lower and the IL-10 level was higher in the P + AP group compared to P group (p < .05). In the P + AP group, the IL-1β level increased in the second week and decreased in the fourth week (p < .05), the number of blood vessels was high in the gingival and periodontal ligament in the second and fourth week (p < .05); and the number of fibroblasts in the gingival tissue was low in the fourth week, and higher in the periodontal tissue in both period (p < .05). Regarding bone remodeling, the RANK and RANKL levels decreased in the P + AP group (p < .05). The OPG level did not differ between the P and P + AP groups (p > .05), but decreased from the second to the fourth experimental week in P + AP group (p < .05). The treatment of experimental periodontitis with atmospheric plasma for 4 weeks modulated the inflammatory response to favor the repair process and decreased the bone resorption biomarkers, indicating a better control of bone remodeling in periodontal disease.

A Comparative Analysis of the Efficacy and Safety of Nimesulide/Paracetamol Fixed-Dose Combination With Other NSAIDs in Acute Pain Management: A Randomized, Prospective, Multicenter, Active-Controlled Study (the SAFE-2 Study).

Objective In this study, we aimed to compare the efficacy and safety of the fixed-dose combination (FDC) of nimesulide (100 mg) + paracetamol (325 mg) [NP], ketorolac (10 mg) [Kt] alone, diclofenac (50 mg) + paracetamol (325 mg) [DP], and aceclofenac (100 mg) + paracetamol (325 mg) [AP] in patients with acute painful conditions. Methods This was a randomized, prospective, open-label, multicentre, active-controlled study involving patients aged ≥18 years, with acute painful conditions like low back pain, acute musculoskeletal disorders, and trauma such as tendinitis, tenosynovitis, bursitis, sprains and strains, migraine, dental pain, painful dental procedures, and post-surgical pain. Reduction in pain intensity and liver, renal, gastrointestinal, and cardiovascular safety were assessed on days seven and14. Results A total of 600 patients were randomized into NP, Kt, DP, and AP groups in a 1:1:1:1 ratio. NP, DP, and AP were administered twice a day while Kt was given three times a day. The reduction of pain as measured by the numerical rating scale (NRS) scores at the end of day seven was 3.75 ± 1.58 in the NP group, 2.96 ± 1.18 in the Kt group, 3.42 ± 1.42 in the DP group, and 3.47 ± 1.30 in the AP group. The pain reduction in the NP group was significantly greater (p<0.001) as compared to the Kt group and non-inferior to the DP and AP groups on days seven and 14. Non-inferiority was concluded between the NP, DP, and AP groups as the lower limit of 95% CI of the difference in the change of pain intensity on both days seven and14 was above the predefined margin of -1.0. All the drugs were well tolerated, but a significantly greater number of adverse events were reported in the DP group (32) as compared to the NP group (14)(p<0.05). The most common adverse events reported during the study were nausea, gastritis, and abdominal pain in all four groups. There was no significant alteration in liver and renal function tests except a rise in serum creatinine in the DP group. Conclusions The FDC of nimesulide with paracetamol is superior to ketorolac and non-inferior to the FDC of diclofenac with paracetamol and aceclofenac with paracetamol in the management of pain in patients with acute painful conditions. The tolerability profile of the FDC of nimesulide with paracetamol is similar to that of ketorolac but better than diclofenac with paracetamol and aceclofenac with paracetamol combinations.

Efficacy and safety of anlotinib plus anti-PD-1 agents in patients with refractory advanced biliary tract cancers.

Anlotinib has demonstrated promising anti-tumor efficacy in various solid tumors. Additionally, there is evidence suggesting that immune therapy can enhance the systemic responses of anlotinib. This study aimed to assess the effectiveness and safety of combining anlotinib with PD-1 inhibitors compared to fluoropyrimidine-based chemotherapy as a second-line treatment option for advanced biliary tract cancers (BTCs). A total of 242 patients with BTCs were screened at the First Affiliated Hospital of Zhengzhou University from October 2015 to October 2022. Among them, 78 patients who received either anlotinib plus PD-1 inhibitors (AP) or fluoropyrimidine-based chemotherapy (FB) as second-line treatment were included in the study. The primary endpoint was progression-free survival (PFS), and the secondary endpoints included objective response rate (ORR), disease control rate (DCR), overall survival (OS), safety, and predictive tumor biomarkers. Among the 78 patients with BTCs, 39 patients received AP, while 39 patients were administered FB. The ORR in the AP group was 20.5%, compared to 5.1% in the FB group. The DCR was 87.2% in the AP group and 66.7% in the FB group. The AP group demonstrated significantly better ORR and DCR compared to the FB group (p=0.042, p=0.032). The median PFS and OS in the AP group were 7.9months (95% CI: 4.35-11.45) and 13.9months (95% CI: 5.39-22.41), respectively. In the FB group, the median PFS and OS were 4.1months (95% CI: 3.17-5.03) and 13.2months (95% CI: 8.72-17.68), respectively. The AP group exhibited significantly better median PFS than the FB group (p=0.027). In the subgroup analysis, patients without liver metastasis had a much longer PFS in the AP group compared to the FB group (14.3 vs. 5.5months, p=0.016). Similarly, patients with CEA≤5μg/L also demonstrated a longer PFS in the AP group compared to the FB group (8.7 vs. 3.9months, p=0.008). The combination of anlotinib and PD-1 inhibitors demonstrated a promising clinical effect compared to fluoropyrimidine-based chemotherapy in the second-line treatment of refractory advanced BTCs. Liver metastases and CEA levels may serve as predictive factors for identifying patients who may benefit from AP therapy.

Hippocampal HDAC6 promotes POCD by regulating NLRP3-induced microglia pyroptosis via HSP90/HSP70 in aged mice

BackgroundPostoperative Cognitive Dysfunction (POCD) has attracted increased attention, but its precise mechanism remains to be explored. This study aimed to figure out whether HDAC6 could regulate NLRP3-induced pyroptosis by modulating the functions of HSP70 and HSP90 in microglia to participate in postoperative cognitive dysfunction in aged mice. MethodsAnimal models of postoperative cognitive dysfunction in aged mice were established by splenectomy under sevoflurane anesthesia. Morris water maze was used to examine the cognitive function and motor ability. Sixteen-months-old C57BL/6 male mice were randomly divided into six groups: control group (C group), sham surgery group (SA group), splenectomy group (S group), splenectomy + HDAC6 inhibitor ACY-1215 group (ACY group), splenectomy + HDAC6 inhibitor ACY-1215 + HSP70 inhibitor Apoptozole group (AP group), splenectomy + solvent control group (SC group). The serum and hippocampus of mice were taken after mice were executed. The protein levels of HDAC6, HSP90, HSP70, NLRP3, GSDMD-N, cleaved-Caspase-1 (P20), IL-1β were detected by western blotting. Serum IL-1β, IL-6 and S100β were measured using ELISA assay, and cell localization of HDAC6 was detected by immunofluorescence. In vitro experiments, BV2 cells were used to validate whether this mechanism worked in microglia. The protein levels of HDAC6, HSP90, HSP70, NLRP3, GSDMD-N, P20, IL-1β were detected by western blotting and the content of IL-1β in the supernatant was measured using ELISA assay. The degree of acetylation of HSP90, the interaction of HSP70, HSP90 and NLRP3 were analyzed by coimmunoprecipitation assay. ResultsSplenectomy under sevoflurane anesthesia in aged mice could prolong the escape latency, reduce the number of crossing platforms, increase the expression of HDAC6 and activate the NLRP3 inflammasome to induce pyroptosis in hippocampus microglia. Using ACY-1215 could reduce the activation of NLRP3 inflammasome, the pyroptosis of microglia and the degree of spatial memory impairment. Apoptozole could inhibit the binding of HSP70 to NLRP3, reduce the degradation of NLRP3 and reverse the protective effect of HDAC6 inhibitors. The results acquired in vitro experiments closely resembled those in vivo, LPS stimulation led to the pyroptosis of BV2 microglia cells and the release of IL-1β due to the activation of the NLRP3 inflammasome, ACY-1215 showed the anti-inflammatory effect and Apoptozole exerted the opposite effect. ConclusionsOur findings suggest that hippocampal HDAC6 promotes POCD by regulating NLRP3-induced microglia pyroptosis via HSP90/HSP70 in aged mice.